Multicenter Study Evaluating the Relationship Between Perceived Daily Stress Level and Glycemic Level in Subjects With Type 1 Diabetes (EVASTRESS)

Type 1 diabetes (T1D) affects around 200,000 people in France. The only treatment is insulin, administered either by multiple injections, by pump alone or, more recently, by automated insulin delivery systems (AIDs), which have resulted in a very significant improvement in glycaemic control and quality of life. These closed-loop (CL) devices are capable of effectively regulating the conventional factors associated with glycaemic disturbance, namely dietary intake and physical activity. However, they do not account of stress, which some subjects with T1D perceive as a major disrupter of their blood sugar levels. One of the reasons for this is undoubtedly that stress, unlike diet or physical activity, cannot be anticipated. Since stress is difficult to predict, it is also more difficult to study. Its onset, intensity, duration and progression are linked to the subject's experience, psychological state and environment. Not all patients respond to stress triggers in the same way. Some patients appear to be more reactive than others to these agents, particularly when they are exposed to them chronically or repeatedly, in an anxiety-provoking environment. This is known as chronic psychosocial stress, and it is this type of stress that seems to be most closely associated with glycaemic disturbance in subjects with T1D, most often in the form of hyperglycaemia and, more rarely, hypoglycaemia. However, there are no solid epidemiological or experimental data to support these observations.

The study we propose is a prospective multicentre clinical trial in 125 subjects with T1D treated with insulin pumps or multi-injections at 14 French university centres. Our aim is to evaluate the relationship between interstitial glucose levels measured by CGM and perceived stress, assessed 4 times a day, away from mealtimes in order to avoid the impact of dietary glycaemia, using a "stressometer". This stressometer is an application designed by CERITD that can be downloaded to the patient's smartphone and consists of an electronic visual analogue scale (VAS) on which the level of stress felt is evaluated quantitatively (continuous value between 0 and 10).

Study Overview

• Status: Suspended
• Conditions: Diabetes Type 1
• Intervention / Treatment: Behavioral: Assess stress levels 4 times a day before meals (morning, noon and evening and at bedtime) using a visual analogue scale

• Study Type: Interventional
• Enrollment (Estimated): 125
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Angers, France, 49100
    • Angers University Hospital
  • Avignon, France, 84000
    • Avignon Hospital
  • Bordeaux, France, 33075
    • Bordeaux University Hospital
  • Brest, France, 29200
    • Brest University Hospital
  • Dijon, France, 21079
    • Dijon University Hospital
  • Grenoble, France, 38043
    • Grenoble University Hospital
  • La Rochelle, France, 17000
    • St Louis Hospital
  • Lille, France, 59037
    • Lille University Hospital
  • Lyon, France, 69008
    • DiabeCare diabetes centre
  • Marseille, France, 13003
    • European Hospital
  • Mérignac, France, 33700
    • Private practice in endocrinology and metabolic diseases
  • Rennes, France, 35200
    • Rennes University Hospital
  • Strasbourg, France, 67091
    • Strasbourg University Hospital
  • Évry, France, 91058
    • CERITD (Centre d'Etudes et de Recherches pour l'Intensification du Traitement du Diabète)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient with a clinical diagnosis of type 1 diabetes of at least 1 year, as determined by the medical record;
• Patient aged at least 18 years;
• Patient treated with an external insulin pump for at least 2 months or with multi-injections;
• Patient with a smartphone compatible with iOS 15.0 or higher or Android 12.0 or higher;
• Patient with a smartphone with Bluetooth 5.0 or higher;
• Patient with HbA1c ≤ 10% with measurement ≤3 months;
• Patient with no psychiatric pathology that could interfere with the study;
• Patient having signed the free and informed consent form to participate in the study;
• Patient affiliated to the French Social Security system;
• Patient agreeing not to eat between meals for the duration of the study (except for hypoglycaemia and/or snacks during physical activity);
• Patient agrees to wear an Empatica EmbracePlus watch for the duration of the study and to charge it according to the device's requirements for recording data;
• Patient agreed to wear an OURA ring for the duration of the study and to recharge it as required by the device to enable data recording (patients at the CERITD centre only).

Exclusion Criteria:

• Type 2 diabetic patient;
• Patient fitted with a closed loop (or artificial pancreas);
• Patient with any characteristic pathology that could interfere with the study (renal failure, unstabilised diabetic retinopathy, heart failure, heart attack within 6 months prior to inclusion, severe neuropathy, particularly autonomic neuropathy);
• Patients with a tendency to snack;
• Patients undergoing treatment with drugs known to significantly interfere with blood sugar levels or the adrenergic system, such as corticosteroids and beta-blockers;
• Patients undergoing atropine treatment (Hydroxyzine Chlorhydrate or Atarax®...), likely to modify the EDA (Electrodermal Activity) ;
• Patients with a known allergy to latex (watch EmbracePlus);
• Pregnant woman;
• Nursing woman;
• Persons deprived of their liberty by judicial or administrative decision, persons under psychiatric care;
• Persons under guardianship or trusteeship or subject to a legal protection measure
• Persons who are not affiliated to a social security scheme or are beneficiaries of such a scheme.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Visual analog scale to measure stress levels	Behavioral: Assess stress levels 4 times a day before meals (morning, noon and evening and at bedtime) using a visual analogue scale; In addition to stress assessment with the stress meter, patients will be fitted with a Continious Glucose Monitoring

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between perceived daily stress, self-assessed on a multi-daily basis using a mobile subjective stress assessment application called a "stress meter", and blood glucose levels measured by continuous glucose monitoring (CGM)	Visual analogue scale to assess stress levels: 0: I feel absolutely no stress 10: I feel extremely stressed	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HbA1c measurement	HbA1c measurement at inclusion	At Inclusion
Characterization of 4 patient profiles according to the impact of daily stress on glycemic control	Questionnaire for Assessing the Impact of Stress on Blood Sugar Levels. This questionnaire was designed and developed by CERITD to assess the impact of perceived stress on blood glucose levels in T1DM patients.	At inclusion
Number of days the Continuous subcutaneous Glucose Monitoring (CGM) worn		14 days
Percentage of time the CGM is active (recommended at least 70% of the time)		14 days
Percentage of sensor time in glucose level measured by the Dexcom One+ CGM time	Percentage of time spent within the target 70-180 mg/dl (3.9-10.0 mmol/L) (TIR); Percentage of time <54 mg/dl (<3.0 mmol/L); Percentage of time spent in the range 54-69 mg/dl (3.0-3.8 mmol/L); Percentage <70 mg/dl (<3.9 mmol/L); Percentage of time >250 mg/dl (>13.9 mmol/L); Percentage of time spent in the range 181-250 mg/dl (10.1-13.9 mmol/L); Percentage of time >180 mg/dl (>10.0 mmol/L)	14 days
Variability of the CGM glucose level	The glycemic variation coefficient (CV) intra patient CV≤36%, CV > 36%	14 days
Glucose management Indicator (GMI)		14 days
Average CGM glucose level	Measurement of glucose by CGM	14 days
Glycaemic evolution over a period during which stress is measured.	Measurement of the area under the curve (AUC) for blood glucose	14 days
Glycaemic evolution over a period during which stress is measured.	Measurement of the maximum blood sugar	14 days
Glycaemic evolution over a period during which stress is measured.	Measurement of the blood sugar delta	14 days
Glycaemic evolution over a period during which stress is measured.	Measurement of the blood sugar average	14 days
Measuring heart rate with the Empatica EmbracePlus watch		14 days
Measuring heart rate variability with the Empatica EmbracePlus watch		14 days
Measuring electrodermal activity with the Empatica EmbracePlus watch		14 days
Measuring heart rate with the Oura ring		14 days
Measuring heart rate variability with the Oura ring		14 days
Measuring accelerometry parameters with the Empatica EmbracePlus watch		14 days
Measuring accelerometry parameters with the Oura ring		14 days
Measuring the amount of sleep you get with the Empatica EmbracePlus watch	"Sleep detection" parameter	14 days
Measuring the amount of sleep you get with the Oura ring	sleep score	14 days
Measuring total sleep time with the Oura ring		14 days
Assessment of sleep quality	Visual Analogue Sleep Scale filled in each morning with reference to the previous night 0: I slept very badly 10: I slept very well	14 days
Measurement of sleep characteristics with the Oura ring	Sleep efficiency as a percentage	14 days
Measurement of inflammatory biomarkers		at inclusion and after 14 days
Capillary cortisol measurement	Hair cortisol levels measured at the end of study.	After 14 days
Assessment of diabetes-related distress in the test population .	PAID (Problem Areas in Diabetes) is a self-administered 5-item scale. Each item is scored from 0 (not a problem) to 4 (serious problem).	at inclusion
Assessment of stress levels using the STAI questionnaire	State-Trait Anxiety Inventory (STAI)-Y1: The STAI-Y1 is composed of 20 items. This questionnaire assesses how the patient feels at the present moment. Patients are asked to score each question on a four-point scale (from 1 -corresponding to "not at all" to 4 - "much").	At inclusion and after 14 days
Assessment of stress levels using the STAI questionnaire	State-Trait Anxiety Inventory STAI-Y2 (anxiety score): The STAI-Y2 is composed of 20 items. This questionnaire assesses how the patient feels in general. Patients are asked to answer each question on a four-point scale (from 1 - corresponding to "almost never" to 4 -"almost always")	After 14 days
Assessment of diabetes-related distress in the test population .	DDS T1 is an indicator of overall diabetes distress (average of 17 items, rated 1 to 6 on a scale). A higher score indicates higher distress.	at inclusion and after 14 days
Evaluation of the perception of hypoglycaemia in the population tested with Clarke score	The Clarke questionnaire is comprised of eight questions to evaluate the hypoglycemia awareness. The answer for each individual question will represent a score (0 or 1). These scores will be summed together to a final score from 0 to 7, representing from normal to minimal/no hypoglycemia awareness.	at inclusion
Evaluation of the perception of hypoglycaemia in the population tested with Gold score	The Gold method is used to assess impaired awareness of hypoglycemia. The scale is from 1 to 7. A score of 4 or more indicates impaired awareness of hypoglycemia	at inclusion
Assessment of stress levels using the PSS-14 questionnaire (Perceived Stress Scale 14)	It is a five-point Likert-type scale and consists of 14 items. Participants rate each item on a scale ranging from "Never (0)" to "Very often (4)". Seven of the items with positive statements are scored in reverse. As the scores obtained from the scale increase, the perceived stress level of the person increases. PSS-14 scores range from 0 to 56, with 0-35 point range indicating normal stress level, 35-56 point range indicating that the individual is under stress	at inclusion and after 14 days
Assessment of stress levels : depression score	The Depression, Anxiety and Stress Scale 21 (DASS-21) is an inventory that will be used to identify the presence and intensity of depressive, anxiety and stress. For depression the cutoff scores are: Normal: 0-9, Mild: 10-12, Moderate:13-20, Severe: 21-27, and Extremely severe: 28-42.	After 7 days
Assessment of stress levels : anxiety score	The Depression, Anxiety and Stress Scale 21 (DASS-21) is an inventory that will be used to identify the presence and intensity of depressive, anxiety and stress. For anxiety the cutoff scores are: Normal: 0-6, Mild: 7-9, Moderate: 10-14, Severe:15-19, and Extremely severe: 20-42.	After 7 days
Assessment of stress levels : stress score	The Depression, Anxiety and Stress Scale 21 (DASS-21) is an inventory that will be used to identify the presence and intensity of depressive, anxiety and stress. For stress the cutoff scores are: Normal: 0-10, Mild:11-18, Moderate:19-26, Severe: 27-34, and Extremely severe: 35-42.	After 7 days
Diagnosis and measurement of the severity of depression: Patient Health Questionnaire (PHQ-9)	The Patient Health Questionnaire (PHQ-9) will be used to assess depressive symptoms, including suicidal ideation, over the last two weeks (9 questions). Items are scored 0-3, resulting in a total score of 0-27. Higher scores indicate more symptoms of depression.	After 7 days
Personality traits : Big Five Inventory 10 (BFI-10)	Items range from 1 (strongly approves) to 5 (strongly disapproves). Scales: openness to experience, conscientiousness, extraversion, agreeableness and neuroticism	After 7 days
Bortner scale	The Bortner self-assessment questionnaire consists of 14 items. It is used to classify individuals according to types of behaviour (A and B)	After 7 days
Quality of life assessment: Short Form 36 questionnaire (SF-36)	Short Form 36 (SF-36) -ranges between 0 (maximum disability) and 100 (no disability). The SF36 score can be converted to utility scores using values within the questionnaire.	After 14 days
Assessment of sleep quality: Pittsburgh Sleep Quality Index (PSQI)	Pittsburgh Sleep Quality Index (PSQI), a self-report questionnaire comprising seven component scores (subjective sleep quality, sleep latency, duration of sleep, sleep efficiency habits, sleep disturbances, use of sleeping medication, and daytime dysfunction), is used to evaluate sleep quality over the last month	After 14 days

Collaborators and Investigators

• Sponsor: Centre d'Etudes et de Recherche pour l'Intensification du Traitement du Diabète
• Investigators: Principal Investigator: Sylvia Franc, MD, Centre d'Etudes et de Recherche pour l'Intensification du Traitement du Diabète

Study record dates

Study Major Dates

• Study Start (Actual): April 22, 2025
• Primary Completion (Estimated): December 5, 2026
• Study Completion (Estimated): December 5, 2026

Study Registration Dates

• First Submitted: February 28, 2025
• First Submitted That Met QC Criteria: March 19, 2025
• First Posted (Actual): March 26, 2025

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: stress; glycemic control
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Autoimmune Diseases; Immune System Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 1
• Other Study ID Numbers: 2024-A02296-41

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No